[Research progress on vascular endothelial growth factor C in meningeal lymphatic vessel-mediated clearance of amyloid β-protein].

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the abnormal deposition of amyloid β-protein (Aβ) as a core pathological feature. Meningeal lymphatic vessels are crucial for Aβ clearance, and their dysfunction accelerates AD progression. Vascular endothelial growth factor C (VEGF-C), through activation of vascular endothelial growth factor receptor 3 and downstream pathways, synergistically promotes lymphangiogenesis, enhances lymphatic permeability, and regulates lymphatic fluid flow, thereby improving Aβ clearance efficiency. Genetic factors and aging-related declines in VEGF-C further impair meningeal lymphatic function, creating a vicious cycle. This review summarizes the mechanisms by which VEGF-C regulates the structure and function of meningeal lymphatic to promote Aβ clearance, synthesizes the evidence that genetic factors and aging contribute to meningeal lymphatic dysfunction through their effects on VEGF-C, and discusses the prospects of individualized intervention strategies for Alzheimer's disease based on VEGF-C-mediated modulation of meningeal lymphatics, aiming to provide insights for AD prevention and treatment.